Panic disorder is an illness which is estimated to afflict 1.5-2% of the adult population. The hallmark of panic disorder is the sudden, crescendo panic attack which may be as fleeting as a few minutes in duration, or may persist for over an hour before subsiding. The majority of patients suffering from panic disorder report an average attack frequency (four 4-symptom attacks) of less than one per day, which is true even for many moderate-to-severely ill patients such as those treated in the large Cross-National Collaborative Panic Study (Ballenger, J. C. et al., "Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. I. Efficacy in short-term treatment," Arch Gen Psychiatry, 45:413-422 (1988)).
Current treatment strategies for panic disorder focus on attempts to control and prevent these intermittent, but severe and often disabling panic attacks, and thereby to reduce the associated inter-episode anticipatory anxiety, phobic avoidance, and somatic preoccupations. To accomplish this effectively with drug therapy requires daily doses of high potency benzodiazepines such as alprazolam, or daily doses of antidepressants such as imipramine.
Due to the chronicity of panic disorder, (Wheeler, E. O. et al., "Neurocirculatory asthenia: a 20-year follow-up study of 173 patients," JAMA, 142:878-889 (1950); Coryell, W. et al., "Panic disorder and primary unipolar depression: a comparison of background and outcome," J Affective Disorders, 5:311-317 (1983); Breier A. et al., "Agoraphobia with panic attacks: development, diagnostic stability, and course of illness," Arch Gen. Psychiatry, 43:1029-1036 (1986)) many patients require treatment for many months or years, and still frequently relapse upon drug discontinuation (Noyes R. et al., "Problems with tricyclic antidepressant use in patients with panic disorder or agoraphobia: results of a naturalistic follow-up study," J. Clin. Psychiatry, 50163-169 (1989); Nagy, L. M. et al., "Clinical and medication outcome after short-term alprazolam and behavioral group treatment in panic disorder," Arch Gen Psychiatry, 46:993-999 (1989); Schweizer, E. et al., "Clinical and medication status at one-year follow-up after maintenance treatment of panic disorder," Presented at CINP Congress, Munich, August 1988).
Though drug therapy for panic disorder is generally highly effective, many patients cannot tolerate antidepressant therapy (Noyes, R. et al., "Follow-up study of patients with panic disorder and agoraphobia with panic attacks treated with tricyclic antidepressants," J. Affective Disord, 16:249-257 (1989); Mavissakalian, M. et al., "Imipramine in the treatment of agoraphobia: dose-response relationships," Am J. Psychiatry, 142:1032-1036 (1985)). Similarly, the risk of physical dependence and a withdrawal reaction upon drug discontinuation deters many patients from optimal use of the benzodiazepines for the treatment of panic disorder which can be severely disabling, but intermittent in nature. (Rickels, K. et al., "Chronic therapeutic use of benzodiazepines: I. Effects of abrupt discontinuation," Arch Gen Psychiatry (in press); Schweizer, E. et al., "Chronic therapeutic use of benzodiazepines: II. Effects of gradual taper," Arch Gen. Psychiatry (in press); Roy-Byrne, P. P. et al., "Benzodiazepine withdrawal: overview and implications for the treatment of anxiety," Am J. Med., 84:1041-1052 (1988))